| dc.description.abstract | Ligand-gated ion channels (LGICs) are cell surface integral proteins that mediate the fast neurotransmission
in the nervous system. LGICs require auxiliary subunits for their trafficking, assembly and
pharmacological modulation. Auxiliary subunits do not form functional homomeric receptors, but are
reported to assemble with the principal subunits in order to modulate their pharmacological profiles. For
example, nACh receptors are built at least by co-assemble of ˛ and ˇ subunits, and the neuronal auxiliary
subunits 3 and 5 and muscle type ˇ, ı, , and determine the agonist affinity of these receptors.
Serotonergic 5-HT3B, 5-HT3C, 5-HT3D and 5-HT3E are reported to assemble with the 5-HT3A subunit to
modulate its pharmacological profile. Functional studies evaluating the role of 2 and ı auxiliary subunits
of GABAA receptors have made important advances in the understanding of the action of benzodiazepines,
ethanol and neurosteroids. Glycine receptors are composed principally by ˛1−3 subunits and the auxiliary
subunit ˇ determines their synaptic location and their pharmacological response to propofol and
ethanol. NMDA receptors appear to be functional as heterotetrameric channels. So far, the existence of
NMDA auxiliary subunits is controversial. On the other hand, Kainate receptors are modulated by NETO 1
and 2. AMPA receptors are modulated by TARPs, Shisa 9, CKAMP44, CNIH2-3 auxiliary proteins reported
that controls their trafficking, conductance and gating of channels. P2X receptors are able to associate
with auxiliary Pannexin-1 protein to modulate P2X7 receptors. Considering the pharmacological relevance
of different LGICs auxiliary subunits in the present work we will highlight the therapeutic potential
of these modulator proteins. | |
